US2008004263A1PendingUtilityA1
Ligands of Follicle Stimulating Hormone Receptor and Methods of Use Thereof
Individually held — no corporate assignee on recordPriority: Mar 4, 2004Filed: Mar 3, 2005Published: Jan 3, 2008
Est. expiryMar 4, 2024(expired)· nominal 20-yr term from priority
A61P 15/08A61P 15/10C07D 417/14
37
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Claims
Abstract
The present invention relates to compounds Formula I (I) that are modulators of the follicle stimulating hormone (FSH) receptor and are useful in the treatment of infertility and related disorders.
Claims
exact text as granted — not AI-modified1 . A compound of Formula I:
or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein:
Ar 1 is aryl, heteroaryl, biaryl, biheteroaryl, arylheteroaryl or heteroarylaryl, wherein Ar 1 is optionally substituted with one or more substituents selected from halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, carbocyclyl optionally substituted by one or more R 13 , heterocyclyl optionally substituted by one or more R 13 , carbocyclylalkyl optionally substituted by one or more R 13 , carbocyclylalkenyl optionally substituted by one or more R 13 , carbocyclylalkynyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 ;
Ar 2 is aryl or heteroaryl, each optionally substituted with one or more substituents selected from halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, carbocyclyl optionally substituted by one or more R 14 , heterocyclyl optionally substituted by one or more R 14 , hydroxylamino, OR 9 , SR 9 , SOR 10 , SO 2 R 10 , COR 10 , COOR 9 , OC(O)R 10 or NR 11 R 12 ;
D is N, C or CR 3 ;
is a single bond when D is N or CR 3 ;
is a double bond when D is C;
A 1 is absent or a C 1-3 straight-chain aliphatic group optionally substituted with one or more substituents selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, (C 1-6 alkyl)amino, di(C 1-6 alkyl)amino, hydroxy, carboxy, (C 1-4 alkoxy)carbonyl, or cyano;
A 2 is C 1-4 straight-chain aliphatic group optionally substituted with one or more substituents selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, (C 1-6 alkyl)amino, di(C 1-6 alkyl)amino, hydroxy, carboxy, (C 1-4 alkoxy)carbonyl, or cyano;
E is CO, C(O)O, C(O)NR 4 , NR 4 CONR 4 , SO, SO 2 , SONR 4 , SO 2 NR 4 , or a bond;
G is C 1-3 alkylene, C 2-3 alkenylene or C 2-3 alkynylene optionally substituted with one or more substituents selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, hydroxy, carboxy, (C 1-4 alkoxy)carbonyl, or cyano;
R 1 is H, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, wherein R 1 is optionally substituted with one or more substituents selected from halo, OH, SH, nitro, cyano, C 1-4 haloalkyl, C 1-5 acyl, C 1-5 acyloxy, C 1-4 alkoxy, C 1-4 thioalkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, aminocarbonyl, (C 1-4 alkyl)aminocarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 haloalkylsulfinyl, C 1-4 haloalkylsulfonyl, aminosulfonyl, (C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, ureido, C 1-4 alkylureido, di(C 1-4 alkyl)ureido, thioureido, C 1-4 alkylthioureido, di(C 1-4 alkyl)thioureido, carboxy, (C 1-6 alkoxy)carbonyl, and hydroxylamino;
R 2 is H, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, wherein R 2 is optionally substituted with one or more substituents selected from halo, OH, SH, nitro, cyano, C 1-4 haloalkyl, C 1-5 acyl, C 1-5 acyloxy, C 1-4 alkoxy, C 1-4 thioalkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, aminocarbonyl, (C 1-4 alkyl)aminocarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 haloalkylsulfinyl, C 1-4 haloalkylsulfonyl, aminosulfonyl, (C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, ureido, C 1-4 alkylureido, di(C 1-4 alkyl)ureido, thioureido, C 1-4 alkylthioureido, di(C 1-4 alkyl)thioureido, carboxy, (C 1-6 alkoxy)carbonyl, and hydroxylamino;
or R 1 and R 2 together with the carbon atoms to which they are attached and the two carbon atoms through which the isoxazole and thiazole moieties of the core are joined form a fused C 5-7 carbocyclyl group or fused 5-7 membered heterocyclyl group optionally substituted with one or more substituents selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, hydroxy, carboxy, (C 1-4 alkoxy)carbonyl, or cyano;
R 3 is H or C 1-6 alkyl;
R 4 , at each independent occurrence, is H or C 1-4 alkyl;
R 5 and R 9 are each, independently, H, C 1-8 alkyl, C 1-8 haloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, aryl, heteroaryl, C 3-7 cycloalkyl, 5-7 membered heterocycloalkyl, arylalkyl, heteroarylalkyl, (C 3-7 cycloalkyl)alkyl or (5-7 membered heterocycloalkyl)alkyl;
R 6 and R 10 are each, independently, H, C 1-8 alkyl, C 1-8 haloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, aryl, heteroaryl, C 3-7 cycloalkyl, 5-7 membered heterocycloalkyl, arylalkyl, heteroarylalkyl, (C 3-7 cycloalkyl)alkyl, (5-7 membered heterocycloalkyl)alkyl, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino,
R 7 and R 8 are each, independently, H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, aryl, heteroaryl, C 3-7 cycloalkyl, 5-7 membered heterocycloalkyl, arylalkyl, heteroarylalkyl, (C 3-7 cycloalkyl)alkyl, (5-7 membered heterocycloalkyl)alkyl, (C 1-8 alkyl)carbonyl, (C 1-8 haloalkyl)carbonyl, (C 1-8 alkoxy)carbonyl, (C 1-8 haloalkoxy)carbonyl, (C 1-4 alkyl)sulfonyl, (C 1-4 haloalkyl)sulfonyl or arylsulfonyl;
or R 7 and R 8 , together with the N atom to which they are attached form a 5-7 membered heterocycloalkyl group;
R 11 and R 12 are each, independently, H, C 1-8 alkyl, C2-g alkenyl, C 2-8 alkynyl, aryl, heteroaryl, C 3-7 cycloalkyl, 5-7 membered heterocycloalkyl, arylalkyl, heteroarylalkyl, (C 3-7 cycloalkyl)alkyl, (5-7 membered heterocycloalkyl)alkyl, (C 1-8 alkyl)carbonyl, (C 1-8 haloalkyl)carbonyl, (C 1-8 alkoxy)carbonyl, (C 1-8 haloalkoxy)carbonyl, (C 1-4 alkyl)sulfonyl, (C 1-4 haloalkyl)sulfonyl or arylsulfonyl;
or R 11 and R 12 , together with the N atom to which they are attached form a 5-7 membered heterocycloalkyl group; and
R 13 and R 14 are each, independently, halo, cyano, nitro, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, hydroxy, carboxy, (C 1-4 alkoxy)carbonyl, C 1-4 acyl, C 1-4 acyloxy, aminocarbonyl, (C 1-4 alkyl)aminocarbonyl, or di(C 1-4 alkyl)aminocarbonyl.
2 . The compound of claim 1 wherein Ar 1 is aryl, heteroaryl, biaryl, biheteroaryl, arylheteroaryl or heteroarylaryl, wherein Ar 1 is substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, carbocyclyl optionally substituted by one or more R 13 , heterocyclyl optionally substituted by one or more R 13 , carbocyclylalkyl optionally substituted by one or more R 13 , carbocyclylalkenyl optionally substituted by one or more R 13 , carbocyclylalkynyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 .
3 . The compound of claim 1 wherein Ar 1 is aryl, heteroaryl, biaryl, biheteroaryl, arylheteroaryl or heteroarylaryl, wherein Ar 1 is optionally substituted with one or more substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 .
4 . The compound of claim 1 wherein Ar 1 is aryl, biaryl or heteroarylaryl, wherein Ar 1 is optionally substituted with one or more substituents selected from halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, carbocyclyl optionally substituted by one or more R 13 , heterocyclyl optionally substituted by one or more R 13 , carbocyclylalkyl optionally substituted by one or more R 13 , carbocyclylalkenyl optionally substituted by one or more R 13 , carbocyclylalkynyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 .
5 . The compound of claim 1 wherein Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is optionally substituted with one or more substituents selected from halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl optionally substituted by one or more R 13 , heterocyclyl optionally substituted by one or more R 13 , carbocyclylalkyl optionally substituted by one or more R 13 , carbocyclylalkenyl optionally substituted by one or more R 13 , carbocyclylalkynyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 .
6 . The compound of claim 1 wherein Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is optionally substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 .
7 . The compound of claim 1 wherein Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , C 1-4 alkoxy, SO 2 R 6 , COR 6 , COOR 5 or NR 7 R 8 .
8 . The compound of claim 1 wherein Ar 2 is aryl or heteroaryl, each optionally substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, carbocyclyl optionally substituted by one or more R 14 , heterocyclyl optionally substituted by one or more R 14 , hydroxylamino, OR 9 , SR 9 , SOR 10 , SO 2 R 10 , COR 10 , COOR 9 , OC(O)R 10 or NR 11 R 12 .
9 . The compound of claim 1 wherein Ar 2 is aryl or heteroaryl.
10 . The compound of claim 1 wherein Ar 2 is heteroaryl.
11 . The compound of claim 1 wherein Ar 2 is thienyl.
12 . The compound of claim 1 wherein Ar 2 is aryl.
13 . The compound of claim 1 wherein Ar 2 is phenyl.
14 . The compound of claim 1 wherein D is CR 3 .
15 . The compound of claim 1 wherein D is CH.
16 . The compound of claim 1 wherein A 1 is a C 1-3 alkylene group.
17 . The compound of claim 1 wherein A 1 is CH 2 or CH 2 CH 2 .
18 . The compound of claim 1 wherein A 1 is absent.
19 . The compound of claim 1 wherein D is CR 3 and A 2 is a C 1-3 alkylene group.
20 . The compound of claim 1 wherein D is CR 3 and A 2 is CH 2 CH 2 or CH 2 CH 2 CH 2 .
21 . The compound of claim 1 wherein D is CR 3 , A 1 is CH 2 CH 2 , and A 2 is CH 2 CH 2 .
22 . The compound of claim 1 wherein D is CR 3 , A 1 is absent, and A 2 is CH 2 CH 2 CH 2 .
23 . The compound of claim 1 wherein E is CO, C(O)O, C(O)NR 4 , SO 2 or a bond.
24 . The compound of claim 1 wherein E is CO or SO 2 .
25 . The compound of claim 1 wherein E is CO.
26 . The compound of claim 1 wherein G is C 1-3 alkylene.
27 . The compound of claim 1 wherein G is CH 2 or CH 2 CH 2 .
28 . The compound of claim 1 wherein G is CH 2 .
29 . The compound of claim 1 wherein R 1 is H or C 1-4 alkyl.
30 . The compound of claim 1 wherein R 1 is methyl.
31 . The compound of claim 1 wherein:
R 1 is H, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, wherein R 1 is optionally substituted with one or more substituents selected from halo, OH, SH, nitro, cyano, C 1-4 haloalkyl, C 1-5 acyl, C 1-5 acyloxy, C 1-4 alkoxy, C 1-4 thioalkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, aminocarbonyl, (C 1-4 alkyl)aminocarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 haloalkylsulfinyl, C 1-4 haloalkylsulfonyl, aminosulfonyl, (C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, ureido, C 1-4 alkylureido, di(C 1-4 alkyl)ureido, thioureido, C 1-4 alkylthioureido, di(C 1-4 alkyl)thioureido, carboxy, (C 1-6 alkoxy)carbonyl, and hydroxylamino; and R 2 is H, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, wherein R 2 is optionally substituted with one or more substituents selected from halo, OH, SH, nitro, cyano, C 1-4 haloalkyl, C 1-5 acyl, C 1-5 acyloxy, C 1-4 alkoxy, C 1-4 thioalkoxy, C 1-4 haloalkoxy, amino, (C 1-4 alkyl)amino, di(C 1-4 alkyl)amino, aminocarbonyl, (C 1-4 alkyl)aminocarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 haloalkylsulfinyl, C 1-4 haloalkylsulfonyl, aminosulfonyl, (C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, ureido, C 1-4 alkylureido, di(C 1-4 alkyl)ureido, thioureido, C 1-4 alkylthioureido, di(C 1-4 alkyl)thioureido, carboxy, (C 1-6 alkoxy)carbonyl, and hydroxylamino.
32 . The compound of claim 1 wherein R 2 is H or C 1-4 alkyl.
33 . The compound of claim 1 wherein R 2 is H.
34 . The compound of claim 1 wherein R 3 is H.
35 . The compound of claim 1 wherein R 4 , at each independent occurrence, is H.
36 . The compound of claim 1 wherein:
D is CR 3 ; A 1 is a absent or a C 1-3 alkylene group; A 2 is a C 1-3 alkylene group; E is CO, C(O)O, C(O)NR 4 , SO 2 or a bond; G is C 1-3 alkylene; R 1 is H or C 1-6 alkyl; and R 2 is H or C 1-6 alkyl.
37 . The compound of claim 1 wherein:
Ar 2 is aryl or heteroaryl, each optionally substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl optionally substituted by one or more R 14 , heterocyclyl optionally substituted by one or more R 14 , hydroxylamino, OR 9 , SR 9 , SOR 10 , SO 2 R 10 , COR 10 , COOR 9 , OC(O)R 10 or NR 11 R 12 ; D is CR 3 ; A 1 is absent or a C 1-3 alkylene group; A 2 is a C 1-3 alkylene group; E is CO, C(O)O, C(O)NR 4 , SO 2 or a bond; G is C 1-3 alkylene; R 1 is H or C 1-6 alkyl; and R 2 is H or C 1-6 alkyl.
38 . The compound of claim 1 wherein:
Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is optionally substituted with one or more substituents selected from halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl optionally substituted by one or more R 13 , heterocyclyl optionally substituted by one or more R 13 , carbocyclylalkyl optionally substituted by one or more R 13 , carbocyclylalkenyl optionally substituted by one or more R 13 , carbocyclylalkynyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 ; Ar 2 is aryl or heteroaryl; D is CR 3 ; A 1 is absent or a C 1-3 alkylene group; A 2 is a C 1-3 alkylene group; E is CO, C(O)O, C(O)NR 4 , SO 2 or a bond; G is C 1-3 alkylene; R 1 is H or C 1-6 alkyl; and R 2 is H or C 1-6 alkyl.
39 . The compound of claim 1 wherein:
Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is optionally substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 ; Ar 2 is aryl or heteroaryl; D is CR 3 ; A 1 is absent or a C 1-3 alkylene group; A 2 is a C 1-3 alkylene group; E is CO, C(O)O, C(O)NR 4 , SO 2 or a bond; G is C 1-3 alkylene; R 1 is H or C 1-6 alkyl; and R 2 is H or C 1-6 alkyl.
40 . The compound of claim 1 wherein:
Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is optionally substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkyl optionally substituted by one or more R 13 , heterocyclylalkenyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , hydroxylamino, OR 5 , SR 5 , SOR 6 , SO 2 R 6 , COR 6 , COOR 5 , OC(O)R 6 or NR 7 R 8 ; Ar 2 is aryl or heteroaryl; D is CH; A 1 is absent, CH 2 or CH 2 CH 2 ; A 2 is CH 2 CH 2 or CH 2 CH 2 CH 2 ; E is CO, SO 2 or a bond; G is CH 2 or CH 2 CH 2 ; R 1 is C 1-4 alkyl; and R 2 is H.
41 . The compound of claim 1 wherein:
Ar 1 is phenyl, biphenyl or heteroarylphenyl, wherein Ar 1 is substituted with 1, 2 or 3 substituents selected from halo, cyano, nitro, heterocyclyl optionally substituted by one or more R 13 , heterocyclylalkynyl optionally substituted by one or more R 13 , C 1-4 alkoxy, SO 2 R 6 , COR 6 , COOR 5 or NR 7 R 8 ; Ar 2 is aryl or heteroaryl; D is CH; A 1 is absent, CH 2 or CH 2 CH 2 ; A 2 is CH 2 CH 2 or CH 2 CH 2 CH 2 ; E is CO, SO 2 or a bond; G is CH 2 or CH 2 CH 2 ; R 1 is C 1-4 alkyl; and R 2 is H.
42 . The compound of claim 1 selected from:
4-{4-[3-(3-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-1-phenylmethane-sulfonyl-piperidine; 1-(4-{4-[3-(3-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 1-(4-{4-[3-(3-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-3-yl-ethanone; 1-(2-{4-[3-(3-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-pyrrolidin-1-yl)-2-thiophen-2-yl-ethanone; 1-(4-{4-[3-(3-Isopropylamino-phenyl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 1-[4-(4-{5-Methyl-3-[3-(2-morpholin-4-yl-ethylamino)-phenyl]-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone; 1-(4-{4-[5-Methyl-3-(3-morpholin-4-yl-phenyl)-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 1-[4-(4-{5-Methyl-3-[3-(4-methyl-piperazin-1-yl)-phenyl]-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone; N-[3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-yl]-acetamide; N-[3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-3-yl]-acetamide; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carboxylic acid amide; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-3-carboxylic acid amide; 3′-{5-Methyl-4-[2-(1-phenylmethanesulfonyl-piperidin-4-yl)-thiazol-4-yl]-isoxazol-3-yl}-biphenyl-4-carboxylic acid; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carboxylic acid; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-pyrrolidin-2-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carboxylic acid; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-3-carboxylic acid; 1-(4-{4-[5-Methyl-3-(3-pyridin-4-yl-phenyl)-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 1-(4-{4-[5-Methyl-3-(3-pyrimidin-5-yl-phenyl)isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 1-(4-{4-[3-(4′-Methoxy-biphenyl-3-yl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carboxylic acid dimethylamide; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carboxylic acid methylamide; 1-[4-(4-{5-Methyl-3-[4′-(morpholine-4-carbonyl)-biphenyl-3-yl]-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone; 1-[4-(4-{5-Methyl-3-[3′-(morpholine-4-carbonyl)-biphenyl-3-yl]-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone; 1-(4-{4-[3-(4′-Amino-biphenyl-3-yl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; N-[3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-yl]-methanesulfonamide; 1-(4-{4-[3-(4′-Methanesulfonyl-biphenyl-3-yl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 2,2,2-Trifluoro-N-[3′-(5-methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-3-yl]-acetamide; 1-(4-{4-[3-(3′-Methanesulfonyl-biphenyl-3-yl)-5-methyl-isoxazol-4-yl]-thiazol-2-yl}-piperidin-1-yl)-2-thiophen-2-yl-ethanone; 3′-(5-Methyl-4-{2-[1-(2-thiophen-2-yl-acetyl)-piperidin-4-yl]-thiazol-4-yl}-isoxazol-3-yl)-biphenyl-4-carbonitrile; 1-{4-[4-(3-{3-[3-(1,1-Dioxo-1λ 6 -thiomorpholin-4-yl)-prop-1-ynyl]-phenyl}-5-methyl-isoxazol-4-yl)-thiazol-2-yl]-piperidin-1-yl}-2-thiophen-2-yl-ethanone; 1-[4-(4-{5-Methyl-3-[4′-(1H-tetrazol-5-yl)-biphenyl-3-yl]-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone; and 1-[4-(4-{3-[4′-(4,5-Dihydro-1H-imidazol-2-yl)-biphenyl-3-yl]-5-methyl-isoxazol-4-yl}-thiazol-2-yl)-piperidin-1-yl]-2-thiophen-2-yl-ethanone;
or pharmaceutically acceptable salt thereof.
43 . A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
44 . A method of modulating the follicle stimulating hormone (FSH) receptor comprising contacting said receptor with a compound of claim 1 .
45 . A method of activating the follicle stimulating hormone (FSH) receptor comprising contacting said receptor with a compound of claim 1 .
46 . A method of increasing the adenylyl cyclase activity or the level of 5′-monophosphate (cAMP) in a cell, cell culture or tissue expressing the follicle stimulating hormone receptor comprising contacting said cell, cell culture or tissue with a compound of claim 1 .
47 . A method of inducing ovulation in a female mammal comprising administering to said female mammal an ovulation-inducing amount of a compound of claim 1 .
48 . A method of treating a fertility disorder in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 .
49 . A method of treating infertility in a female patient comprising administering to said female patient a therapeutically effective amount of a compound of claim 1 .
50 . A compound according to any one of claims 1 to 42 for use in therapy.
51 . A compound according to any one of claims 1 to 42 for use in the treatment of a fertility disorder in a patient.
52 . A compound according to any one of claims 1 to 42 for use in the treatment of infertility in a female patient.
53 . A compound according to any one of claims 1 to 42 for use in the preparation of a medicament for use in therapy.
54 . A compound according to any one of claims 1 to 42 for use in the preparation of a medicament for use in the treatment of a fertility disorder in a patient.
55 . A compound according to any one of claims 1 to 42 for use in the preparation of a medicament for use in the treatment of infertility in a female patient.
56 . Use of a compound according to any one of claims 1 to 42 for the manufacture of a medicament.
57 . Use of a compound according to any one of claims 1 to 42 for the manufacture of a medicament for the treatment of a fertility disorder in a patient.
58 . Use of a compound according to any one of claims 1 to 42 for the manufacture of a medicament for the treatment of infertility in a female patient.Join the waitlist — get patent alerts
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